Subchondral Bone Plate Thickening Precedes Chondrocyte Apoptosis and Cartilage Degradation in Spontaneous Animal Models of Osteoarthritis

Abstract

Osteoarthritis (OA) is the most common joint disorder characterised by bone remodelling and cartilage degradation and associated with chondrocyte apoptosis. These processes were investigated at 10, 16, 24, and 30 weeks in Dunkin Hartley (DH) and Bristol Strain 2 (BS2) guinea pigs that develop OA spontaneously. Both strains had a more pronounced chondrocyte apoptosis, cartilage degradation, and subchondral bone changes in the medial than the lateral side of the tibia, and between strains, the changes were always greater and faster in DH than BS2. In the medial side, a significant increase of chondrocyte apoptosis and cartilage degradation was observed in DH between 24 and 30 weeks of age preceded by a progressive thickening and stiffening of subchondral bone plate (Sbp). The Sbp thickness consistently increased over the 30-week study period but the bone mineral density (BMD) of the Sbp gradually decreased after 16 weeks. The absence of these changes in the medial side of BS2 may indicate that the Sbp of DH was undergoing remodelling. Chondrocyte apoptosis was largely confined to the deep zone of articular cartilage and correlated with thickness of the subchondral bone plate suggesting that cartilage degradation and chondrocyte apoptosis may be a consequence of continuous bone remodelling during the development of OA in these animal models of OA.

Histopathological assessment of primary osteoarthritic knees in large patient cohort reveal the possibility of several potential patterns of osteoarthritis initiation

“…There is a need to better understand the complete spectrum of characteristics involved in this heterogeneous disease to improve characterization of knee OA sub-types. [39] In order to do so, we need to clearly document, define and analyze changes in cellular response,[40,41] extracellular matrix,[42–44] tidemark and SCB [45–48] that are important to the structure and function of cartilage. This is an important aspect from therapeutic perspective also, in order to improve the efficacy of the treatments, by identifying various possible OA sub-groups for targeted treatment procedures.…”

Insights on Molecular Mechanisms of Chondrocytes Death in Osteoarthritis

“…Zamli et al underlined that, unlike destabilization of the medial meniscus (DMM) mice model of OA, in which apoptosis was observed in the superficial zone (SZ) and middle zone (MZ), chondrocyte apoptosis in guinea pigs was confined to the deep zone of articular cartilage, perhaps reflecting a different mode of OA induction [122]. Zamli and co-workers further demonstrated that bone remodeling, via subchondral bone plate thickening, preceeded chondrocyte apoptosis and cartilage degradation [123]. …”

“…Furthermore, preserving subchondral bone integrity could be an alternative strategy, as subchondral bone plate thickening seems to be an early event in OA development, which preceded apoptosis of chondrocytes in a longitudinal animal study [123]. Also, therapies dedicated to the reduction of the catabolic phenotype of chondrocytes may protect against post traumatic OA [124].…”

Development of a microcomputed tomography scoring system to characterize disease progression in the Hartley guinea pig model of spontaneous osteoarthritis

“…Advantages of microCT include 3-dimensional visualization of the joint (vs. 2-dimensional views on histology), the ability to evaluate living specimens in a longitudinal fashion, and more sensitive detection of subtle bony lesions that tend to occur early in OA disease progression(26,27). As discussed further, below, it is advantageous that these multiplanar reconstructions of the intact organ can be made in an endless number of angles for complete evaluation of the entire joint.…”